Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients.

The intraperitoneal route may offer more physiological insulin delivery through absorption of a proportion of the dose into the portal circulation. We have compared 1-h square-wave and bolus supplemental infusions of a fixed dose of 10 U of intraperitoneal insulin in 6 C-peptide negative insulin-dependent diabetic patients eating a standard breakfast and compared the insulin, glucose and metabolite responses with those of non-diabetic control subjects. Blood glucose profiles were similar on the two experimental days and although the peak glucose levels were not different from normal they were delayed by 30 min (p<0.05). Basal free insulin levels were elevated in diabetic patients (square-wave 19.6±2.3, bolus 18.7±1.9mU/l) compared to controls (7.3±1.0mU/l, p< 0.02) and rose more rapidly after bolus injection than infusion. Peak insulin concentration was achieved at 33±4 min after bolus, 90±13 min after infusion (p<0.02) and 39±5 min in normal control subjects. The shape of the profile of free insulin concentration was similar after bolus injection and in the controls, but after square-wave infusion the return to baseline was delayed (p< 0.05). Fasting intermediary metabolite concentrations were normal on both study days in the patients, but serum cortisol levels were significantly elevated and glucagon concentrations low. Metabolite responses to the meal were not significantly different from normal after bolus injection but increases in lactate and glycerol were seen at some time points between 60 and 180 min after infusion. Glucagon levels remained low after square-wave infusion. We conclude that bolus injection of the breakfast insulin supplement gives a more optimal profile of insulin delivery for patients on intraperitoneal insulin.